There is an expected increased incidence of chronic hepatitis C virus infection (HCV) in the Unites States within the next years, with subsequent increased risks of liver damage, including fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma and end-stage liver disease requiring liver transplantation. This disease is/will be the source of enormous health care costs and morbidity/mortality. Most hepatologists still rely on liver biopsy findings in patients newly diagnosed with HCV, which enables the assessment of liver damage (fibrosis and inflammation). Liver biopsy has limitations, including cost, invasiveness, poor patient acceptance, limited sampling, inter-observer variability and is difficult to repeat. Non invasive tests to capture the extent of liver damage at a larger scale are urgently needed. These will gain more acceptance among patients and hepatologists. In this proposal, we would like to test and validate non invasive magnetic resonance imaging (MRI) methods based on advanced diffusion (intravoxel incoherent motion diffusion MRI: IVIM DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) for the detection of fibrosis and cirrhosis in HCV patients. Based on our recent preliminary data, we believe that the combination of IVIM DW- and DCE-MRI has potential for detection of fibrosis and cirrhosis with excellent accuracy, while enabling coverage of the whole liver. In order to improve the diagnostic performance of MRI, we would like to build and validate a predictive model based on advanced functional MRI metrics (diffusion and perfusion). If validated, this novel non invasive algorithm will not only decreases the number of liver biopsies, but also enable earlier diagnosis of liver fibrosis when antiviral treatment is more effective, and enable a comprehensive evaluation of the liver (to assess for cirrhosis, portal hypertension and hepatocellular cancer). This could significantly reduce the cost of care, could become a useful tool for testing new antifibrogenic and antiviral drugs in HCV, and could be used to follow patients for detection of progression to cirrhosis. This will be a highly significant progress in liver diseases given the increased burden of HCV in this country, and would benefit a large number of Americans over the next decade. PUBLIC HEALTH RELEVANCE: Patients with hepatitis C virus infection (HCV) are at high risk of developing liver scarring (fibrosis), with ultimate risks of cirrhosis and liver cancer that may require liver transplant. We would like to develop non invasive advanced MRI techniques (diffusion and dynamic contrast-enhanced MRI) to assess the degree of liver damage in HCV. These techniques combined could reach high diagnostic performance for detection of liver fibrosis; and could decrease the number of necessary liver biopsies, which have risks and sample only a small portion of the liver.